This is a proposal to conduct a two arm randomized effectiveness trial investigating whether a task shifting/sharing model of treating depression and improving adherence to ART in patients who fail first line antiretroviral therapy (ART) can occur using nurses in South Africa trained in CBT. South Africa is the country with the highest number of HIV infections in the world and the highest number of HIV/AIDS-related deaths,5-7 and where access to third line ART treatment is not currently available in the public healthcare system. Clinical depression, like elsewhere, is one of the highest comorbidities to HIV/AIDS, with estimated rates up to 34.9 percent.8 Depression, in the context of HIV, leads to poor self-care behavior such as non-adherence to ART and worse retention in care, which are critical for treatment success.9 Preliminary work. The U.S. based investigators have developed and successfully tested an approach integrating adherence counseling into cognitive- behavioral therapy for depression in HIV.10,11 The South. Africa based team, in collaboration with the U.S. based team, has conducted preliminary work to evaluate the cultural appropriateness and feasibility of integrating this approach into the South African HIV treatment setting. Accordingly, we have 1) conducted an open-pilot of the treatment in Cape Town with 6 HIV-infected patients with depression using a clinical psychology PhD student as the therapist, 2) conducted formative qualitative research on the manifestation of depression and ways to adapt this approach for the South Africa HIV care setting,12 3) successfully trained two clinic nurses in the adapted version of the intervention, and 4) completed an open pilot feasibility trial with 14 patients with these nurses as interventionists. Design: The current study builds on our successful feasibility pilot. Given that CBT is a validated treatment for depression, and that dissemination of evidenced-based interventions in HIV is a noted priority,13,14 we propose a two-arm effectiveness RCT (stratified by antidepressant medication initiation/use or not) of nurse-delivered cognitive behavioral therapy for depression and adherence integrated into the HIV primary care setting in S. Africa. To ensure that those who need this intervention the most will receive it, participants will be patients with HIV who have failed first line ART, and have a unipolar depressive mood disorder. Primary outcomes (Aim 1) include adherence to ART (assessed by WisePill), depression (assessed by an independent evaluator), and proportion of (second line) treatment failures in each condition. Comparing this integrated care model to usual care (enhanced adherence counseling for first-line treatment-failures in this setting), will allow for an incremental cost-effectiveness analysis in Aim 2. We will collect resource utilization and cost data to examine the cost- effectiveness of reduced depression, and potentially, better HIV outcomes. Before study start-up, and twice a year, we will convene community advisory meetings of HIV patients as well as stakeholders (clinic directors, Nurses AIDS service NGO leaders) to maximize the chances of uptake scalability of the model should it be successful.